The DOI matches its Crossref record; 71 of the 71 references it cites were found in a registry or an index.
Statistically significant meta-analyses of clinical trials have modest credibility and inflated effects
Abstract
Objective To assess whether nominally statistically significant effects in meta-analyses of clinical trials are true and whether their magnitude is inflated.Study design and setting Data from the Cochrane Database of Systematic Reviews 2005 (issue 4) and 2010 (issue 1) were used. We considered meta-analyses with binary outcomes and four or more trials in 2005 with P<0.05 for the random-effects odds ratio (OR). We examined whether any of these meta-analyses had updated counterparts in 2010. We estimated the credibility (true-positive probability) under different prior assumptions and inflation in OR estimates in 2005.Results Four hundred sixty-one meta-analyses in 2005 were eligible, and 80 had additional trials included by 2010. The effect sizes (ORs) were smaller in the updating data (2005-2010) than in the respective meta-analyses in 2005 (median 0.85-fold, interquartile range [IQR]: 0.66-1.06), even more prominently for meta-analyses with less than 300 events in 2005 (median 0.67-fold, IQR: 0.54-0.96). Mean credibility of the 461 meta-analyses in 2005 was 63-84% depending on the assumptions made. Credibility estimates changed >20% in 19-31 (24-39%) of the 80 updated meta-analyses.Conclusions Most meta-analyses with nominally significant results pertain to truly nonnull effects, but exceptions are not uncommon. The magnitude of observed effects, especially in meta-analyses with limited evidence, is often inflated.
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“If anything, summary effects from meta-analyses, including power estimates calculated from meta-analysis results, may also be modestly inflated 22 .”
From Power failure: why small sample size undermines the reliability of neuroscience (2013) · cites this paper as [22]
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Power failure: why small sample size undermines the reliability of neuroscience
Button, K. S., Ioannidis, J. P. A., Mokrysz, C., Nosek, B. A., Flint, J., Robinson, E. S. J., & Munafò, M. R. (2013) · Nature Reviews Neuroscience · doi:10.1038/nrn3475 · Cited by 7,641
Self-citationIncreasing value and reducing waste in research design, conduct, and analysis
Ioannidis, J. P. A., Greenland, S., Hlatky, M. A., Khoury, M. J., Macleod, M. R., Moher, D., Schulz, K. F., & Tibshirani, R. (2014) · The Lancet · doi:10.1016/s0140-6736(13)62227-8 · Cited by 1,597
Self-citationHow to increase value and reduce waste when research priorities are set
Chalmers, I., Bracken, M. B., Djulbegovic, B., Garattini, S., Grant, J., Gülmezoglu, A. M., Howells, D. W., Ioannidis, J. P. A., & Oliver, S. (2014) · The Lancet · doi:10.1016/s0140-6736(13)62229-1 · Cited by 1,436
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Head, M. L., Holman, L., Lanfear, R., Kahn, A. T., & Jennions, M. D. (2015) · PLOS Biology · doi:10.1371/journal.pbio.1002106 · Cited by 1,388
“However, meta-analyses are only as good as the data they use, and a recent study estimated that up to 37% of meta-analyses of clinical trials reporting a significant mean effect size represent false positives [34].”
BackgroundTrial Sequential Analysis in systematic reviews with meta-analysis
Wetterslev, J., Jakobsen, J. C., & Gluud, C. N. (2017) · BMC Medical Research Methodology · doi:10.1186/s12874-017-0315-7 · Cited by 1,216
“later [2]; the estimated intervention effects, when further trials are included in the meta-analysis update, become considerably lower than previously estimated [2].”
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Metadata
- Authors
- Pereira, T. V., & Ioannidis, J. P. A.
- Affiliations
- University of Ioannina (GR)
- Tufts University (US)
- Venue
- Journal of Clinical Epidemiology
- Publisher
- Elsevier BV
- Published
- 2011-10
- Volume
- 64
- Issue
- 10
- Pages
- 1060-1069
- ISSN
- 0895-4356 (ISSN-L)
- OpenAlex
- W2004108172
- Cited by
- 160
- References
- 71
- Citations by year
- 2026: 7 · 2025: 12 · 2024: 8 · 2023: 7 · 2022: 5 · 2021: 14 · 2020: 25 · 2019: 7 · 2018: 7 · 2017: 7 · 2016: 11 · 2015: 14 · 2014: 8 · 2013: 13 · 2012: 9
- FWCI
- 2.72
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Clinical Epidemiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministério da Educação
- Fundação de Amparo à Pesquisa do Estado de São Paulo
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
- Topics
- Social Sciences › Decision Sciences › Statistics, Probability and Uncertainty › Meta-analysis and systematic reviews
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Epidemiology
- Keywords
- meta-analysis, statistical significance, effect size inflation, prior assumptions, binary outcomes, odds ratio, limited evidence, Cochrane Database of Systematic Reviews
- MeSH terms
- Clinical Trials as Topic, Health Services Research, Humans, Meta-Analysis as Topic, Bias
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